Study of plasma cyclic nucleotides in normals and patients with hypertension will be done to investigate possible abnormalities in cyclic nucleotide metabolism. Pressor agents such as angiotensin and norepinephrine will be infused and blood pressure and changes in plasma cyclic nucleotide levels correlated in both groups. Similar studies will also be performed in the dog using selected arterio venous catherization. We will continue to develop and use the technique of cyclic nucleotide immunocytochemistry for the localization of cGMP and cAMP in tissues and cells grown in culture. We will correlate cyclic nucleotide levels after pharmacologic or hormonal stimulation with intracellular localization by immunocytochemistry and with the physiologic response of the tissue to the stimulus. Such studies will include the mechanism of action of acetylcholine in brain and heart, angiotensin on smooth muscle, serum factors on cell growth, pituitary hormone secretion by releasing factors, and ACTH on adrenal cortical growth regulation. Immunocytochemistry will also be adapted for the ultrastructural localization of cAMP and cGMP. We will also attempt to determine by radioimmunoassay and by immunocytochemistry whether cIMP and other purine cyclic nucleotides are present in mamallian tissues and whether they have physiologic roles.